Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study

Author(s): Tara Sanft, MD^1,2; Maura Harrigan, RD, MS, CSO³; Courtney McGowan, RD, CSO³; Brenda Cartmel, PhD^2,3; Michelle Zupa, BS³; Fang-Yong Li, MS³; Leah M. Ferrucci, PhD^2,3; Leah Puklin, MPH³; Anlan Cao, BS³; Thai Hien Nguyen, MPH³; Marian L. Neuhouser, PhD⁴; Dawn L. Hershman, MD⁵; Karen Basen-Engquist, PhD⁶; Beth A. Jones, PhD^2,3; Tish Knobf, PhD^3,7; Anees B. Chagpar, MD, MPH^1,2; Andrea Silber, MD^1,2; Anna Tanasijevic, MPH⁸; Jennifer A. Ligibel, MD⁹; Melinda L. Irwin, PhD, MPH^1,2

Source: https://doi.org/10.1200/JCO.23.00871

Dr. Maen Hussein's Thoughts

There have been studies showing decreased recurrence in women who underwent curative breast surgeries (walking and yoga). This study assesses if it will affect the intensity of chemotherapy delivered. Although it did not affect it, women who underwent the program had better pathologic complete response (pCR), we need more studies to assess role of nutrition and exercise in treating cancer as we develop a wholesome approach to treat our patients, something we may be able to do in our practice.

PURPOSE

Successful completion of chemotherapy is critical to improve breast cancer outcomes. Relative dose intensity (RDI), defined as the ratio of chemotherapy delivered to prescribed, is a measure of chemotherapy completion and is associated with cancer mortality. The effect of exercise and eating a healthy diet on RDI is unknown. We conducted a randomized trial of an exercise and nutrition intervention on RDI and pathologic complete response (pCR) in women diagnosed with breast cancer initiating chemotherapy.

METHODS

One hundred seventy-three women with stage I-III breast cancer were randomly assigned to usual care (UC; n = 86) or a home-based exercise and nutrition intervention with counseling sessions delivered by oncology-certified registered dietitians (n = 87). Chemotherapy dose adjustments and delays and pCR were abstracted from electronic medical records. T-tests and chi-square tests were used to examine the effect of the intervention versus UC on RDI and pCR.

RESULTS

Participants randomly assigned to intervention had greater improvements in exercise and diet quality compared with UC (P < .05). RDI was 92.9% ± 12.1% and 93.6% ± 11.1% for intervention and UC, respectively (P = .69); the proportion of patients in the intervention versus UC who achieved ≥85% RDI was 81% and 85%, respectively (P = .44). The proportion of patients who had at least one dose reduction and/or delay was 38% intervention and 36% UC (P = .80). Among 72 women who received neoadjuvant chemotherapy, women randomly assigned to intervention were more likely to have a pCR than those randomly assigned to UC (53% v 28%; P = .037).

CONCLUSION

Although a diet and exercise intervention did not affect RDI, the intervention was associated with a higher pCR in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative and triple-negative breast cancer undergoing neoadjuvant chemotherapy.

Author Affiliations

¹Yale University School of Medicine, New Haven, CT; ²Yale Cancer Center, New Haven, CT; ³Yale School of Public Health, New Haven, CT; ⁴Fred Hutchinson Cancer Research Center, Seattle, WA; ⁵Columbia University Medical Center, New York, NY; ⁶The University of Texas MD Anderson Cancer Center, Houston, TX; ⁷Yale School of Nursing, New Haven, CT; ⁸Dana-Farber Cancer Institute, Boston, MA; ⁹Dana-Farber Cancer Institute, Boston, MA

PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor–Negative Metastatic Breast Cancer

Findings from the PACE study show that the addition of Palbociclib to Fulvestrant was not better than Fulvestrant alone, and the addition of Avelumab to Fulvestrant improved and nearly doubled the PFS. This is compelling and should be studied further for our patients with HR+ HER2- MBC.

Ribociclib plus Endocrine Therapy in Early Breast Cancer

For your stage II – III HR+, HER2-neg breast cancer patients. Adjuvant Ribociclib + AI showed a ~3% invasive DFS benefit vs. an AI alone (90 vs 87%). This is a 3-year treatment protocol as opposed to 5 years of an AI, which some patients may appreciate.

Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial

This is a study showing tumor agnostic activity of trastuzumab deruxtecan (T-DXd) with an all-comer overall response rate (ORR) of 37.1%, duration of response (DOR) of 11.3 months and an overall survival (OS) of 13.4 months in an otherwise heavily pre-treated group. Those with IHC-3+ derived larger benefit than 2+. Patients with ERBB2 mutations who had no expression of HER2 were excluded from the trial.

Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial

This is a 10-year follow-up of the ShortHER study using nine weeks vs. 12 months of adjuvant trastuzumab in HR+ non-metastatic breast cancer. With long-term follow-up, non-inferiority could not be claimed statistically. Still, the DFS/OS results are identical in those patients with N0-N3 disease, while those with N4 disease seemed to have a significant difference favoring 12 months of therapy, suggesting that volume/burden of disease drives the margin of benefit in adjuvant trastuzumab therapy.

Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial

This is another option for HR positive patients after failing hormonal therapy, with an acceptable toxicity profile. Patients were HER-2 negative. (The study does not indicate if patients were HER-2 low.) It will be interesting to see how this will fair in this population now that there is another option with Enhrtu. Interesting though, patients without visceral metastases did better with chemotherapy.